Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients
Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients
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DOI：
10.3727/096368915x688579
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Garbuzova-Davis, Svitlana
中科院分区：
文献类型：
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作者：
Eve, David J.;Ehrhart, Jared;Garbuzova-Davis, Svitlana
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征在于脊髓和大脑中的运动神经元变性。这种疾病临床表现为逐渐的肌肉无力和萎缩，导致瘫痪和呼吸衰竭死亡。虽然多种相互依赖的因素可能有助于ALS的发病机制，但越来越多的证据表明可能存在促进疾病进展的自身免疫机制。来源于人脐带血（hUCB）的血浆作为治疗工具的潜在用途目前处于起步阶段。hUCB血浆富含造血过程中细胞生长和存活所需的细胞因子和生长因子。本研究通过检测人脐血血浆对ALS患者外周血单个核细胞（MNCs）caspase 3/7表达的影响，探讨人脐血血浆对体外培养的ALS患者外周血单个核细胞（MNCs）增殖和凋亡活性的影响。观察到三种不同的反应，植物血凝素（PHA）诱导的MNCs的增殖，这是独立的年龄，疾病持续时间，和ALS评分量表：组I正常反应PHA，组II显示没有反应PHA，而组III显示出过度活跃的反应PHA。hUCB血浆减弱了多动反应（第III组），并增强了第I组ALS患者的正常反应，但没有改变对PHA无反应者的反应（第II组）。在ALS患者的MNC中观察到的半胱天冬酶3/7的活性升高通过hUCB血浆处理显著降低。因此，研究结果表明，不同的细胞对有丝分裂原的反应表明，在ALS患者的淋巴细胞功能的改变，这可能是一个信号的免疫缺陷的无应答者和自身免疫改变的反应过度。hUCB血浆调节有丝分裂原细胞应答和降低半胱天冬酶活性的能力表明，单独使用hUCB血浆或与干细胞一起使用hUCB血浆可证明可用作ALS患者的治疗剂。
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA)-induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with stem cells, may prove useful as a therapeutic in ALS patients.